Single Nucleotide Polymorphisms in the Hypoxia-Inducible Factor-1 Gene and Colorectal Cancer Risk

被引:41
|
作者
Knechtel, Gudrun [1 ]
Szkandera, Joanna [1 ]
Stotz, Michael [1 ]
Hofmann, Guenter [1 ]
Langsenlehner, Uwe [2 ]
Krippl, Peter [3 ]
Samonigg, Hellmut [1 ]
Renner, Wilfried [4 ]
Langner, Cord [5 ]
Dehchamani, Dadbeh [6 ]
Gerger, Armin [1 ]
机构
[1] Med Univ Graz, Dept Internal Med, Div Oncol, A-8036 Graz, Austria
[2] Steiermaerk Gebietskrankenkasse, Internal Outpatient Dept, Graz, Austria
[3] Reg Hosp Fuerstenfeld, Dept Internal Med, Fuerstenfeld, Austria
[4] Med Univ Graz, Clin Inst Med & Lab Diagnost, A-8036 Graz, Austria
[5] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria
[6] Med Univ Graz, Dept Dent & Maxillofacial Surg, Div Oral & Craniomaxillofacial Surg, A-8036 Graz, Austria
关键词
colorectal cancer; risk; hypoxia-inducible factor-1; polymorphism; ULCERATIVE-COLITIS; HIF-1-ALPHA GENE; FACTOR; 1-ALPHA; BREAST-CANCER; FACTOR-1-ALPHA; POPULATION; CARCINOMA; GROWTH; IMPACT;
D O I
10.1002/mc.20655
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
With an incidence of about 300 000 new cases colorectal cancer (CRC) is the second leading cause of cancer-related death in Europe and the United States. Environmental and genetic factors influence CRC risk. Hypoxia-inducible factor-1 (HIF-1), a heterodimeric protein composed of two subunits, HIF-1 alpha and HIF-1 beta, plays a critical role in oxygen homeostasis and is involved in angiogenesis and cell proliferation. The gene for the HIF-1 alpha subunit (HIF1A) carries two common missense mutations P5825 (rs11549465) and A588T (rs11549467) which both have been related to increased trans-activation capacity of HIF1A. In our case control study we investigated the association between these polymorphisms and CRC risk. We investigated 381 patients with histologically confirmed CRC and 2156 control subjects. HIF1A genotypes were determined by exonuclease (TaqMan) assays. For determination of microvessel density (MVD) tumor sections were stained using a mouse monoclonal antibody recognizing the panendothelial marker CD31. In a multivariate logistic regression analysis including age and sex neither the HIF1A 5825 allele (Odds ratio: 1.204; 95% confidence interval 0.911-1.592; P = 0.193) nor the 588T allele was significantly associated with CRC (Odds ratio: 0.851; 95% confidence interval 0.444-1.631; P = 0.626). However, in an exploratory analysis, the HIF1A 588T allele was associated with tumor localization (P = 0.016) and tumor size (P = 0.003). MVD was similar in tumors of patients carrying HIF1A 588T allele and patients without this rare allele. We conclude that functional polymorphisms in the HIF1A gene do not modify CRC risk but maybe associated with clinic-pathological features of the disease. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:805 / 809
页数:5
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